The proposed research will examine effects of age of first use of marijuana and duration of use on brain function, brain structure, and cognition. Considering that marijuana is the most widely used illicit drug, if chronic use produces brain dysfunction in some marijuana users and this dysfunction is greater in those who begin use earlier during adolescence and use longer, the potential costs to society could be high. Using positron emission tomography and magnetic resonance imaging, we will examine differences of chronic marijuana users from control subjects in baseline regional cerebral blood flow and cognition-related changes in regional cerebral blood flow (in memory, tapping and gambling tests), as well as whole brain blood flow and brain tissue volume and composition. We hypothesize that chronic marijuana users will differ from control subjects and these differences will be more pronounced in marijuana users with earlier ages of first use and longer durations of use. Hypothesized effects of chronic marijuana use on regional cerebral blood flow in posterior cerebellum, prefrontal cortex, and hippocampus are particular foci of the proposed research. If the hypothesized effects occur, they will provide evidence that chronic marijuana use alters brain functioning and that the pronounced brain development that normally occurs during adolescence increases vulnerability to such alterations. Additional, more extensive cognitive tests will be administered in sessions not involving neuroimaging to test the hypothesis that cognitive effects of marijuana use are also more pronounced in individuals with earlier ages of first use and longer durations of use. Groups of subjects will be matched on premorbid intellectual functioning using records of standardized test scores that are available for children educated in virtually all parts of Iowa. No published studies except ours have demonstrated changes in brain function and cognition in chronic marijuana users relative to control subjects matched on premorbid intellectual functioning. When completed, the proposed research will make important additions to knowledge about effects of chronic marijuana use on human brain function, brain structure, and cognition.